The main objective of the proposed research is to develop an effective means of gene transfer for gene therapeutic treatment of lysosomal storage diseases (LSD) in vitro and in vivo. The major obstacles to the transfer of exogenous genes into neuronal cells of the brain is the presence of the blood-brain barrier(BBB). The use of hyperosmolar mannitol has been shown to be effective in the opening of the blood- brain barrier so that macromolecules can enter into the brain. These spaces created in the capillary endothelium are not small enough to permit large particles, such as viruses and liposomes, to leave the capillary lumen. This problem dictates that the vector must be of a small enough caliber to be able to cross the BBB. The synthesis of a chimeric protein that has both DNA binding ability and a high specificity for neuronal cells will result in a molecule specialized for its purpose, but yet still small enough to accomplish its task. Proteins such as human alpha-N-acetylgalactosaminidase B (alpha-Gal B) and the Reovirus S1 protein (RS1) that have specificity for neuronal cells and will be tested. For DNA binding activity poly-L-lysine will be tested. Additionally, since these molecules will be taken into the cell's endosomes, it is expected that an endosome disrupter such as the tetanus toxin fragment C (TTC) will be included. These synthetic vectors will be tested for their effectiveness of neuronal delivery mice and cats.